Currently, many in vitro cell culture techniques exist to provide a method to keep biological cells alive ex vivo over extended time periods. For example, certain techniques include a static culture, manual batch feed in which cells are seeded on a cell culture vessel suspended in media and placed in a temperature- and CO2-controlled incubator. However, such techniques are not ideal for mimicking a true in vivo physiological microenvironment. For example, in a mammalian body, the cellular microenvironment varies considerably from the conditions that can be stimulated in vivo. Therefore, because cells tend to be a product of their microenvironment, the in vivo cultured cells are not a true representative of cells that occur in a physiological environment.
Some solutions to this issue require specialized labware, which is expensive, not commercially available, and/or is particularly suited only for certain applications. Such solutions cannot utilize standard microplate labware, which is widely available for a multitude of laboratory applications. In addition, other solutions are not accessible to light microscopy, contain a limited throughput, contain a limited number of cell wells/chambers (e.g. <12 per microplate footprint), are difficult to handle and/or load cells, lack atmospheric control, lack an ability to control a flow rate, have transient flow rates, have a limited flow duration, have a requirement for re-circulation, have a requirement for mechanical tilting of the plate to extend the duration, and/or do not have independent well control (i.e., all wells undergo identical perfusion treatment).
Accordingly, there exists a continuing need for an in vitro cell culture technique that allows for enhanced control of the cellular microenvironment using standard microplate labware, as well as systems, apparatuses, and the like for carrying out the technique while also being able to integrate with standard microplate labware.